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Institute of Interdisciplinary Research in human and molecular Biology
IRIBHM is part of the Medical School of the Univerité Libre de Bruxelles (ULB) and one of the largest research structures of the university. Founded in the nineteen sixties with the aim of applying an interdisciplinary approach to the study of thyroid pathophysiology, the Institute has thrived over the years into a number of independent groups with diversifying research interests. Presently, about 130 researchers and technicians are working in the Institute over a range of subjects encompassing signal transduction, development, neuroscience, and cancer, using cell and molecular biology approaches. Staff researchers include physicians, physicists, bioinformaticians, (bio)chemists and biologists. The activities of IRIBHM are mainly taking place on the Erasme campus of ULB, in the suburb of Brussels, although the Institute also contributes to the Institut de Biologie Moléculaire et Médicale (IBMM) on the Gosselies campus. The heavy equipment is common to the whole Institute and often shared with other groups of the campus as technical platforms. This includes genomics, proteomics, transgenesis, FACS and confocal microscopy facilities.
Current research programs include the study of : the mechanisms of H2O2 production in thyrocytes, the regulation cAMP and inositolphosphate regulatory cascades by the TSH receptor, structure-function relationships of the TSH receptor, mechanisms of activation of the TSH receptor by the autoantibodies of Graves'disease, control of the proliferation of thyrocytes by cAMP- and growth factor-dependent mechanisms, the regulation of gene expression in thyrocytes by cAMP, the mechanisms responsible for the development of congenital hypothyroidism.
Control of cell proliferation, Cancer
Our group has pioneered the study of thyroid cell proliferation and differentiation and has demonstrated in these cells the existence of three cascades of mitogenic signal transduction, TSH/adenylyl cyclase/cAMP, EGF-HGF/ras/MAPK and phorbol esters/phospholipase C/protein kinase C. The cAMP pathway promotes both proliferation and differentiation within thyrocytes and is causatively involved in goitrogenesis, tumor promotion and generation of hyperfunctional adenomas. The positive regulation of thyroid cell cycle by cAMP is unique as it targets the assembly and activation of complexes of pre-existing cyclin D and CDK4 without involving most of the intermediaries of known mitogenic signaling cascades. Ongoing studies include the identification by molecular biology techniques (PCR-derived methods, microarrays) of new genes regulated by cAMP and the investigation by proteomic approaches and two-hybrids methology of the novel mechanisms of CDK4 activation by cAMP. Extension of this work to thyroid tumors involves the analysis of gene expression profiles in those tissues by the microarray technology.